| Name: |
| Gustavo Arrizabalaga |
| Title: |
| Assistant Professor |
| Degree: |
| Ph.D., 1999, Massachusetts Institute of Technology |
| Phone: |
| (208) 885-6079 |
| Fax: |
| (208) 885-6518 |
| Email: |
| gustavo@uidaho.edu |
| Lab/Office Location: |
| Gibb Hall, Room 136 |
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| Research Interests: |
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Toxoplasma gondii is an obligate intracellular parasite capable of infecting virtually any nucleated cell from a wide range
of mammalian and avian species. Toxoplasma is one of the most widespread and successful protozoan pathogens and is a common parasite
in humans where it has become one of the main opportunistic pathogens in AIDS patients.
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Some of the most devastating effects of infections by intracellular parasites are a direct consequence of their lytic cycle, which
consists of attachment to the host cell, invasion, intracellular replication and egress. Both invasion and egress by the human
pathogen Toxoplasma gondii are essential for infection and survival, involve fluctuation in intracellular [Ca+2],
morphological changes and secretion from various organelles. Egress in particular is an active response to unknown signals and a
process fatal to the host cell. The goal of our lab is to answer the specific questions: “what are the molecular and genetic
elements involved in egress?” and “what are the cues telling the parasite to exit its host cell?” To answer these questions, our lab
utilizes a combination of molecular genetics, cell biology and biochemistry.
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| Toxoplasma gondii parasites growing inside a human fibroblast cell |
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The specific genes directly involved in egress are unknown and previous studies on this process have centered on the analysis of
artificially induced egress. I recently isolated a mutant in ionophore-induced egress (IIE) and identified a
Na+/H+ exchanger (NHE) as the target of the disruption. The characterization of this mutant revealed a
function for NHE in the regulation of intracellular [Ca2+] and in IIE. Further molecular and biochemical characterization
of NHE1 will aid in understanding the role of ion homeostasis in egress as well as invasion.
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The main focus of my research is to use the knowledge gained in the successful identification of an IIE gene and its cellular
function to identify genes required for natural egress by isolating and characterizing mutants in this crucial process. The analysis
of these mutants combined with the further study of previously isolated but uncharacterized IIE mutants will provide a more complete
picture of the genes and events required for successful exit from the host cell. Moreover, the study of Toxoplasma egress, which
involves cytoskeletal rearrangements, organellar secretion and ion fluxes, is likely to shed light not only on this critical
pathogenic event but also on processes relevant to a wide variety of eukaryotic organisms.
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| Selected Publications: |
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Saeij, J., Arrizabalaga, G. and Boothroyd J.C., 2008. A cluster of four surface antigen genes specifically expressed in bradyzoites, SAG2CDXY, plays an important role in Toxoplasma gondii persistence. Immunity and infection, 76(6):2402-10
Lavine, M and Arrizabalaga, G., 2008 Exit from host cells by the pathogenic parasite Toxoplasma gondii does not require motility. Eukaryotic Cell, 7(1): 131-40
Lavine, M.D., Knoll, L.J., Rooney, P.J. and Arrizabalaga, G. 2007. A Toxoplasma gondii mutant defective in responding to calcium fluxes shows reduced in vivo pathogenicity. Molecular and Biochemical Parasitology, Molecular and Biochemical Parasitology, 155(2): 113-122
Fruth, I.A. and Arrizabalaga G., 2007. Toxoplasma gondii: Induction of egress by the potassium ionophore nigericin. International Journal of Parasitology, 37(14): 1559-67
Lavine, M.D., and Arrizabalaga, G., 2007. Invasion and egress by the obligate intracellular parasite Toxoplasma gondii: potential targets for the development of new antiparasitic drugs. Current Pharmaceutical Design 13; 641-651.
Karasov, A, Boothroyd J.C. and Arrizabalaga, G, 2005. Identification and disruption of a rhoptry localized Sodium Hydrogen Exchanger in Toxoplasma gondii. International Journal of Parasitology 35 (3); 285-291
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